Necessity of endogenous GTP derived from glucose-6-phosphate for insulin secretion augmented by glucose under protein kinase A activation.
To investigate the possible involvement of some intracellular metabolic signaling other than the ATP derived from glucose metabolism under protein kinase A (PKA) activation, we measured the insulin secretory capacity stimulated by glucose and other fuel secretagogues using diazoxide-treated pancreatic islets. Under these conditions, we found a signal from a site proximal to glyceraldehyde-3-phosphate (GA-3-P) in the glycolysis to be necessary for glucose-induced insulin secretion. By using several different glycolytic enzyme inhibitors, we found that this proximal signal is derived from glucose-6-phosphate (G-6-P), and that metabolic signaling distal to GA-3-P also is necessary. Mycophenolic acid completely inhibited the augmented glucose-induced insulin secretion, which guanosine could reverse, indicating that the proximal signaling is coupling with endogenous GTP production. In this novel system of metabolic signaling, endogenous GTP derived from G-6-P in the glycolysis elicits the augmentation of glucose-induced insulin secretion under PKA activation in diazoxide-treated pancreatic islets.
Nishimura
M
M
Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Japan.
Ishida
H
H
Tsuura
Y
Y
Kato
S
S
Mizuno
N
N
Fujimoto
S
S
Mukai
E
E
Kajikawa
M
M
Usami
M
M
Seino
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology; D019298:Glucose-6-Phosphate / Q000378:metabolism*; D005986:Glyceraldehyde 3-Phosphate / Q000378:metabolism; D006019:Glycolysis; D006160:Guanosine Triphosphate / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D002121:Calcium Channel Blockers; D007328:Insulin; D015221:Potassium Channels; D005986:Glyceraldehyde 3-Phosphate; D019298:Glucose-6-Phosphate; D006160:Guanosine Triphosphate; D009568:Nitrendipine; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D003981:Diazoxide; D002118:Calcium